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Medical Policy

Policy Num:       05.001.032
Policy Name:     Buprenorphine Implant for Treatment of Opioid Dependence                               
Policy ID:          [5.001.032][Ac / B / M+/ P+][5.01.26]

Last Review:      October 18, 2022
Next Review:      Archived
Issue:                  10:2022

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Buprenorphine Implant for Treatment of Opioid Dependence

Summary

Description

Buprenorphine is a partial μ-opioid agonist used to treat patients with an opioid addiction. Administered transmucosally, buprenorphine can be used with or without naloxone, which is an opioid antagonist. Though effective, a clinical strategy of using transmucosal buprenorphine is prone to nonadherence, diversion, abuse, and accidental misuse. To lower these risks and improve adherence. A buprenorphine (Probuphine) implant has been developed to provide sustained delivery of buprenorphine for up to 6 months via 4 subdermally inserted rods. Probuphine is intended as a maintenance treatment for a select subgroup of opioid-dependent patients who are clinically stable on a low dose of transmucosal buprenorphine (≤8 mg/d). These implants are inappropriate for new treatment recipients and those who do not have sustained and prolonged clinical stability while being maintained on a generic equivalent of buprenorphine.

Summary of Evidence

For individuals who are addicted to opioids but stable on low-to-moderate doses of transmucosal buprenorphine who receive buprenorphine implants, the evidence includes a randomized controlled trial. Relevant outcomes are change in disease status, morbid events, health status measures, medication use, and treatment-related morbidity. In the pivotal trial, the proportion of patients who reported for no more than 2 out of 6 months any evidence of illicit opioid use was similar between the buprenorphine implant arm (63%) and the sublingual buprenorphine arm (64%). The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Additional Information

Not applicable

OBJECTIVE

The objective of this evidence review is to assess the efficacy and safety of buprenorphine implants compared with transmucosal buprenorphine and whether the implant improves the net health outcome-specifically for treating patients who have an opioid addiction yet are clinically stable and on low-to-moderate doses of a transmucosal buprenorphine-containing product.

POLICY

Buprenorphine subdermal implants may be considered medically necessary when all four of the following criteria have been met:

• The individual has been diagnosed with opioid dependence; and

• The individual has been treated with a stable transmucosal buprenorphine dose (≤8 mg/d of a sublingual Subutex or Suboxone tablet or its transmucosal buprenorphine product equivalent) for 3 months or more without any need for supplemental dosing or adjustments; and

• The individual is currently on a maintenance dose^a of 8 mg per day or less of a sublingual Subutex or Suboxone tablet or its transmucosal buprenorphine product equivalent to achieve sustained prolonged clinical stability on transmucosal buprenorphine; and

• Buprenorphine implants are used as part of a comprehensive substance use disorder treatment program that includes counseling and psychosocial support.

^a U.S. Food and Drug Administration indications specify that maintenance doses should not be tapered to a lower dose for the sole purpose of transitioning to buprenorphine implants (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204442s006lbl.pdf).

Buprenorphine implants are considered investigational for all other indications, including but not limited to:

• When the medically necessary criteria above have not been met;

• For new entrants to treatment;

• For individuals who have not achieved and sustained prolonged clinical stability while being maintained on buprenorphine 8 mg or less per day of a Subutex or Suboxone sublingual tablet or generic equivalent;

• For individuals not enrolled in a comprehensive substance use disorder treatment program;

• Treatment for longer than 12 months.

Individuals can be transitioned back to transmucosal buprenorphine-containing medications for continued treatment after 12 months as needed. Retreatment with buprenorphine implant after a prior 12-month treatment period is considered investigational and not medically necessary under all circumstances.

The prescribing information also provides guidance on acceptable doses of transmucosal buprenorphine that demonstrating stable maintenance dosing (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204442s006lbl.pdf):

• Buprenorphine (Subutex) sublingual tablet (generic equivalent) 8 mg or less per day;

• Buprenorphine and naloxone (Suboxone) sublingual tablet (generic equivalent) 8 mg/2 mg or less per day;

• Buprenorphine and naloxone (Bunavail) buccal film 4.2 mg/0.7 mg or less per day;

• Buprenorphine and naloxone (Zubsolv) sublingual tablets 5.7 mg/1.4 mg or less per day.

Additionally, the prescribing information includes the following factors in determining clinical stability and suitability for Probuphine treatment (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204442s006lbl.pdf):

• Period free from illicit opioid drug use;

• Stability of living environment;

• Participation in a structured activity/job;

• Consistent participation in recommended behavioral therapy/peer support program;

• Consistent compliance with clinic visit requirements;

• Minimal to no desire or need to use illicit opioids;

• Period without episodes of hospitalizations (addiction or mental health issues), emergency room visits, or crisis interventions;

• Social support system.

POLICY GUIDELINES

Inserting up to 4 buprenorphine implants once in each arm at an interval of 6 months may be considered medically necessary.

Coding

Please see the Codes table for details.

BENEFIT APPLICATION

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Buprenorphine implants are likely to produce outcomes equivalent to transmucosal buprenorphine; however, the implants may be more costly. Some plans may use a definition of "medical necessity" that reads similar to the following statement: "A medically necessary service must not be more costly than an alternative service or sequence of services that is at least as likely to produce equivalent health outcomes." In these cases, when it is determined that a strategy using buprenorphine implants is more costly than 1 using sublingual buprenorphine (as determined by plan pricing, provider charges, and/or other mechanisms), then buprenorphine implants may be considered not medically necessary for maintenance therapy of opioid dependence in patients who have achieved and sustained prolonged clinical stability.

For contracts that do not use this definition of medical necessity, benefit or contract language describing the "least costly alternative" may also be applicable for this choice of treatment.

BACKGROUND

Opioid Misuse

Opioids were involved in 49,860 overdose deaths in 2019 (70.6% of all drug overdose deaths).^1,

Treatment

Buprenorphine is among the main options in a medication-assisted treatment strategy for opioid dependence. Transmucosal buprenorphine products have a potential for diversion to an illicit drug market and have resulted in accidental poisonings of small children.^2, To minimize the misuse, Braeburn Pharmaceuticals developed Probuphine, an implantable buprenorphine that would be difficult to divert or abuse, and therefore would less likely be accidentally ingested by children. Further, as an implant, it would maximize adherence passively for 6 or 12 months.

The initial new drug application, submitted by Braeburn in October 2012, sought approval of buprenorphine implants for initial treatment of patients with opioid dependence after just a few days of titration on a transmucosal formulation. The U.S. Food and Drug Administration issued a complete response letter for this new drug application, stating that, although the two 6-month trials met the prespecified end points, the dose provided by the implant "was too low to provide effective treatment for patients new to buprenorphine treatment."^3, However, data from a subset of patients revealed that 4 buprenorphine implants yielded buprenorphine concentrations similar to those observed with sublingual buprenorphine (anywhere from 4 to 8 mg based on average exposure [eg, mean area under the receiver operating characteristic curve values] or concentration). Thus, a subset of patients stabilized on sublingual buprenorphine 8 mg or less could benefit from buprenorphine implants, which is the current target population for which these implants are approved.

Regulatory Status

On May 26, 2016, buprenorphine implant (Probuphine®; Braeburn Pharmaceuticals; NDA 204442) was approved by the U.S. Food and Drug Administration through the new drug application process for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of an agent containing transmucosal buprenorphine (ie, doses of ≤8 mg/d of SubutexÒ or Suboxone® [Indivior] sublingual tablet or generic equivalent). In May 2018, Titan Pharmaceuticals, Inc. was granted exclusive rights to commercialize and develop Probuphine®. On October 19, 2020, Titan Pharmaceuticals discontinued sales of buprenorphine implant for financial reasons.^4,

RATIONALE

This evidence review was created in October 2016 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through May 16, 2022.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Population Reference No. 1 Policy Statement

Buprenorphine

Clinical Context and Therapy Purpose

The purpose of buprenorphine implants in patients who are addicted to opioids but stable on low-to-moderate doses of transmucosal buprenorphine is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of buprenorphine implants improve the net health outcome in patients addicted to opioids but stable on low-to-moderate doses of transmucosal buprenorphine?

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is patients addicted to opioids and stabilized on low-to-moderate doses of transmucosal buprenorphine.

Interventions

The therapy being considered is buprenorphine implants.

Comparators

The following therapy is currently being used to make decisions about opioid addiction: transmucosal buprenorphine.

Outcomes

The general outcomes of interest are a reduction in medication use and adverse events. Follow-up screening is conducted periodically after buprenorphine implantation and explantation. Explantation of the buprenorphine rods is performed at or before 6 months.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded

Review of Evidence

Pivotal Trial Overview

Evidence of the clinical efficacy of buprenorphine implants for the current U.S. Food and Drug Administration (FDA) approved indication comes from a randomized, double-blind, double-dummy, active-controlled, multicenter trial (PRO-814). The trial evaluated the safety and efficacy of 4 buprenorphine 80-mg implants in adult outpatients with opioid dependence who were receiving sublingual buprenorphine 8 mg or less and considered clinically stable by their treating health care provider.^3,5,

The trial included individuals ages 18 to 65 years who met DSM-IV criteria for opioid dependence as a primary diagnosis. These individuals were screened (for up to 3 weeks) and then randomized to sublingual buprenorphine tablets (≤8 mg/d) plus 4 placebo implants or 4 buprenorphine 80-mg implants plus daily sublingual placebo tablets for 24 weeks, and they were then tracked during a 2-week follow-up phase. Supplemental dosing with sublingual buprenorphine plus naloxone tablets was permitted in both treatment arms. Clinical stability was confirmed using the following criteria at randomization: (1) individuals must have been on sublingual buprenorphine treatment for at least 6 months (≥24 weeks); (2) individuals must have been on a stable sublingual buprenorphine dose of 8 mg per day or less for at least the last 90 days; and (3) individuals must not have tested positive on a urine toxicology test for illicit opioids in the last 90 days. Trial-eligible individuals were also required to be free from significant withdrawal symptoms (Clinical Opiate Withdrawal Scale score ≤5).

Individuals were excluded from the trial if they:

• required opioid treatment for a current chronic pain condition or had a nonopioid dependence;

• had elevated hepatic enzyme, bilirubin, or creatinine levels;

• had low platelets or were on coagulopathy or anticoagulant treatment;

• had recent scarring or tattoos on upper arms, or keloid scarring;

• used CYP3A4 inhibitors;

• had an AIDS diagnosis; or

• had other medical or psychiatric conditions (as determined at the investigators' discretion).

The primary efficacy end point was the proportion of responders defined as any patient with no more than 2 out of 6 months with any evidence of illicit opioid use. Evidence of illicit opioid use was defined as either a positive opioid urine toxicology test result or self-reported illicit opioid use. Trial participants provided 10 urine tests each-6 during the monthly visits and 4 randomly scheduled.

The trial was designed to test the noninferiority of the buprenorphine implant compared with sublingual buprenorphine. According to investigators' assumptions, the buprenorphine implant would be noninferior to sublingual buprenorphine if the lower bound of the 95% confidence interval (CI) for the implant's responder rate treatment difference was less than the noninferiority margin of 20%.^6,7, However, because the assumptions used to calculate the noninferiority margin differed from the observed data, FDA, in its final approval of buprenorphine implants, did not permit a claim of noninferiority even though the lower bound of treatment difference was less than 20% The FDA approved label only provides a descriptive analysis of the data.^8,

Pivotal Trial Results

A total of 177 individuals were randomized; of these, 176 received study medication and 173 were included in the modified intention-to-treat analysis by the sponsor. There were no significant differences in the baseline characteristics between the 2 study arms. Overall, patients' mean age was 39 years, 59% were male, 95% were white, and the primary opioid of abuse was as a prescription pain reliever. The median time since the first reported use of opioids was 11.3 years, time since the first diagnosis was 6.2 years, and median duration of buprenorphine treatment was 2.8 years. The study completion rate was 93% (81/87) in the buprenorphine implant arm and 94% (84/90) in the sublingual buprenorphine arm.^3,5,

In the FDA approved label, response rates in the buprenorphine implant arm and sublingual buprenorphine arm were 63% (55/87) and 64% (57/89), respectively, yielding a treatment difference of -1% (95% CI, -15% to 13%).^8, The published report by Rosenthal et al (2016) provided a much higher response rate.^9, In the modified intention-to-treat analysis, the percentages of responders in the respective arms were 96% (81/87) and 88% (78/89%), yielding a treatment difference of 9% (95% CI, 1% to 17%; p=0.03 for the superiority of the implanted over sublingual buprenorphine). In the intention-to-treat analysis, the respective response rates were 93% (81/87) and 88% (78/89), yielding a treatment difference of 6% (95% CI, -3% to 14%; p=0.22 for the superiority of implanted over sublingual buprenorphine).

Differences between the FDA data^3,5, and a 2016 published article^9, relate to the respective approaches to analyzing missing data. In the article, missing data were imputed by taking the mean of the intrasubject positive rate for that treatment arm and then applying a 20% penalty for the buprenorphine implant arm to take a conservative approach. FDA considered missing samples as evidence of opioid use and therefore classified those results as positive. Further, the use of supplemental sublingual buprenorphine in the buprenorphine implant arm was interpreted to indicate that the dose of buprenorphine provided by implant was inadequate for that patient (to maintain stability) and such patients were also classified as positive even if they showed no evidence of opioid use. None of the patients who received rescue doses in the trial required rescue doses in the 6 months before trial entry.

Rosenthal et al (2013)^10, and Ling et al (2010)^11, published two additional studies. They included patients who were new entrants (after just a few days of titration on a transmucosal formulation) to buprenorphine treatment. Both studies were submitted as part of the new drug application in 2013. Although both met their prespecified end points, FDA determined that the dose provided by the implants was too low to be effective for patients new to buprenorphine treatment; therefore, the new drug application was rejected. These studies are not discussed further. The prescribing information explicitly states:

"Probuphine should not be used for individuals who are new entrants to buprenorphine treatment or who have not achieved and sustained prolonged clinical stability on low to moderate doses of a transmucosal buprenorphine-containing product, i.e., doses of no more than 8 mg per day of a Subutex or Suboxone sublingual tablet or generic equivalent, because the dose appears to be too low to be effective in these populations."

Adverse Events

The important potential harms of implant use are the risk of implant migration, protrusion, expulsion, and nerve damage resulting from the procedure. The safety of buprenorphine implants was evaluated in 349 opioid-dependent individuals across 3 double-blind trials (n=309) and 2 open-label extension studies (n=40). In these studies, 258 individuals were exposed to buprenorphine implants for at least 24 weeks, and 82 individuals were exposed for 48 weeks. Adverse events commonly associated with buprenorphine implants (>10% of individuals) were implant-site pain, pruritus, and erythema, as well as non-implant-site related events (≥5%) such as headache, depression, constipation, nausea, vomiting, back pain, toothache, and oropharyngeal pain.^8,

Summary of Evidence

For individuals who are addicted to opioids but stable on low-to-moderate doses of transmucosal buprenorphine who receive buprenorphine implants, the evidence includes a randomized controlled trial. Relevant outcomes are change in disease status, morbid events, health status measures, medication use, and treatment-related morbidity. In the pivotal trial, the proportion of patients who reported for no more than 2 out of 6 months any evidence of illicit opioid use was similar between the buprenorphine implant arm (63%) and the sublingual buprenorphine arm (64%). The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American College of Physicians

in 2017, the American College of Physicians (ACP) published a position paper on health and public policy to facilitate effective prevention and treatment of substance use disorders involving illicit and prescription drugs.^12, ACP made recommendations specific to buprenorphine. As 1 of a number of strategies to address the epidemic of prescription drug misuse, ACP recommended "improved training in the treatment of substance use disorders, including buprenorphine-based treatment" as well as to "lift barriers that impede access to medication to treat opioid use disorder (methadone, buprenorphine, and naltrexone) and to medications for overdose prevention (naloxone)."

American Society of Addiction Medicine

In 2015, the American Society of Addiction Medicine's national practice guidelines on the use of medications to treat addiction involving opioid use published did not include buprenorphine implants.^13, A 2020 focused update of the American Society of Addiction Medicine's 2015 guidelines recommended buprenorphine as treatment for patients with opioid use disorder, who are able to give informed consent and have no specific contraindication for this treatment. Although buprenorphine implants were not specifically recommended, the guideline states that "all FDA approved medications for the treatment of opioid use disorder should be available to all patients" and further states that "the FDA recently approved several new buprenorphine formulations for treatment of opioid use disorder...as data regarding the effectiveness of these products are currently limited, clinicians should use these products as indicated and be mindful of emerging evidence as it becomes available." ^14,

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for buprenorphine implants have been identified.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in July 2022 did not identify any ongoing or unpublished trials that would likely influence this review.

The U.S. Food and Drug Administration, under section 505(o)(3) of the Food, Drug, and Cosmetic Act, has requested that Titan Pharmaceuticals conduct the following postmarketing studies:

• A prospective descriptive observational cohort study of insertion-, localization-, and removal-related serious adverse events and their sequelae associated with buprenorphine implant use. The study should be completed by November 2021.

• As of July 2020, other planned Phase 4 studies have been delayed due to financial constraints:

  • A clinical trial to assess the risk of QT prolongation with buprenorphine implant. The study protocol is under U.S. Food and Drug review.

  • A clinical trial to evaluate the effect of scarring or inflammation related to a prior implant on the safety of reimplantation/reinsertion, the potential for migration of implants, and the bioavailability of buprenorphine when the rods are implanted in a previously used site. Trial commencement is planned for 2021.

• A clinical trial to evaluate the safety, feasibility, and pharmacokinetics of buprenorphine implantation at other body sites. Data collection for this trial is delayed.

• A QT trial using alternative designs as described in ICH E14 Q&A 6.1 in patients who are initiating treatment with buprenorphine in the clinical setting, across the therapeutic dose range.

A search of the U.S. Food and Drug Administration Postmarketing Requirements and Commitments Database in July 2021 identified that "Titan has reported that they are postponing the initiation of the studies intended to address PMRs 3078-1, 3078-3, and 3078-4 by approximately 18 months. https://www.accessdata.fda.gov/Scripts/cder/pmc/index.cfm

References

1. Centers for Disease Control and Prevention. Opioid Overdose: Prescription Opioid Overdose Data. 2018; https://www.cdc.gov/drugoverdose/data/overdose.html. Accessed July 25, 2022.
2. Centers for Disease Control and Prevention (CDC). Emergency department visits and hospitalizations for buprenorphine ingestion by children--United States, 2010-2011. MMWR Morb Mortal Wkly Rep. Jan 25 2013; 62(3): 56. PMID 23344700
3. Food and Drug Administration (FDA). FDA Briefing Materials: Meeting of the Psychopharmacologic Drugs Advisory Committee: PROBUPHINE (buprenorphine hydrochloride subdermal implant) for maintenance treatment of opioid dependence. 2016; https://wayback.archive-it.org/7993/20170405230620/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM480732.pdf. Accessed July 26, 2022.
4. Titan Pharmaceuticals, Inc. Dear Healthcare Professional Letter. October, 2020. https://probuphinerems.com/ Accessed July 25, 2022.
5. Skeete R, Travis J. Efficacy and Safety of Probuphine for the Maintenance Treatment of Opioid Dependence in Clinically Stable Patients. FDA Presentation: Psychopharmacologic Drugs Advisory Committee (PDAC) Meeting January 12, 2016. 2016; https://wayback.archive-it.org/7993/20170405230706/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM482605.pdf. Accessed July 26, 2022
6. Braeburn Pharmaceuticals. PROBUPHINE (buprenorphine HCl/ethylene vinyl acetate) Implant CIII. Treatment of Opioid Dependence. Errata to Briefing Document and Risk Evaluation and Mitigation Strategy. 2016; https://wayback.archive-it.org/7993/20170405230702/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM480735.pdf. Accessed July 27, 2022.
7. Braeburn Pharmaceuticals. Probuphine (Buprenorphine Hydrochloride Implant). Psychopharmacologic Drugs Advisory Committee: January 12, 2016. 2016; https://wayback.archive-it.org/7993/20170405230631/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM480733.pdf. Accessed July 28, 2022.
8. Braeburn Pharmaceuticals. Highlights of Prescribing Information: Probuphine (buprenorphine) implant for subdermal administration CIII. Initial U.S. Approval: 2002. 2016 (revised); https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204442Orig1s000lbl.pdf Accessed July 25, 2022.
9. Rosenthal RN, Lofwall MR, Kim S, et al. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA. Jul 19 2016; 316(3): 282-90. PMID 27434441
10. Rosenthal RN, Ling W, Casadonte P, et al. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. Dec 2013; 108(12): 2141-9. PMID 23919595
11. Ling W, Casadonte P, Bigelow G, et al. Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial. JAMA. Oct 13 2010; 304(14): 1576-83. PMID 20940383
12. Crowley R, Kirschner N, Dunn AS, et al. Health and Public Policy to Facilitate Effective Prevention and Treatment of Substance Use Disorders Involving Illicit and Prescription Drugs: An American College of Physicians Position Paper. Ann Intern Med. May 16 2017; 166(10): 733-736. PMID 28346947
13. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. Sep-Oct 2015; 9(5): 358-67. PMID 26406300
14. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. Mar/Apr 2020; 14(2S Suppl 1): 1-91. PMID 32511106

Codes

Appplicable Modifiers

Policy History